Tolerance of the newborn to antiretroviral drug exposure in utero

Expert Opinion on Drug Safety

Volumn 14, Issue 5, 2015, Pages 643-654

  Sibiude, Jeanne ^a,b   Warszawski, Josiane ^b   Blanche, Stéphane ^c,d  

^a HÔPITAL LOUIS MOURIER   (France)

^b BICÊTRE HOSPITAL   (France)

^c UNIVERSITÉ PARIS DESCARTES   (France)

^d UNIVERSITÉ DE PARIS   (France)

Author keywords

Antiretrovirals; HIV; Pregnancy

Indexed keywords

ANTIRETROVIRUS AGENT; BIOLOGICAL MARKER; CELL NUCLEUS DNA; MITOCHONDRIAL DNA; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; NUCLEOSIDE ANALOG; NUCLEOTIDE DERIVATIVE; PROTEINASE INHIBITOR; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT;

BIRTH; BRAIN DISEASE; CANCER RISK; CARDIOTOXICITY; CHRONIC INFLAMMATION; DISEASE TRANSMISSION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG TOLERANCE; FETUS DISEASE; FIRST TRIMESTER PREGNANCY; GENOTOXICITY; HEALTH CARE ACCESS; HEART FAILURE; HEMATOPOIESIS; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IMAGING; IMMATURITY; INDUSTRIALIZATION; LONG TERM CARE; MACROCYTIC ANEMIA; MITOCHONDRIAL TOXICITY; NEWBORN ASSESSMENT; NEWBORN MORBIDITY; PERINATAL PERIOD; PLACENTAL TRANSFER; PREGNANT WOMAN; PREMATURITY; PRENATAL DRUG EXPOSURE; REVIEW; VULNERABLE POPULATION; ANIMAL; FEMALE; HIV INFECTIONS; HUMAN IMMUNODEFICIENCY VIRUS 1; ISOLATION AND PURIFICATION; NEWBORN; PREGNANCY; PREGNANCY COMPLICATIONS, INFECTIOUS; PREVENTION AND CONTROL; TRANSMISSION; VERTICAL TRANSMISSION; VIROLOGY;

ANIMALS; ANTI-HIV AGENTS; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; INFANT, NEWBORN; INFECTIOUS DISEASE TRANSMISSION, VERTICAL; PREGNANCY; PREGNANCY COMPLICATIONS, INFECTIOUS;

EID: 84928333710     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1517/14740338.2015.1019462     Document Type: Review

References (98)

1. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med 1994;331:1173-80
2. Forbes JC, Alimenti AM, Singer J, et al. A national review of vertical HIV transmission. AIDS 2012;26:757-63
3. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Eng J Med 2011;365:493-505
4. Townsend CL, Byrne L, Cortina-Borja M, et al. Earlier initiation of ART and further decline in mother-to-child HIV transmission rates, 2000-2011. AIDS 2014;28:1049-57
5. Tubiana R, Le Chenadec J, Rouzioux C, et al. Factors associated with mother-to-child transmission of HIV-1 despite a maternal viral load <500 copies/ml at delivery: a case-control study nested in the French perinatal cohort (EPF-ANRS CO1). Cl Infec Dis 2010;50:585-96
6. Siegfried N, van der Merwe L, Brocklehurst P, Sint TT. Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database Syst Rev 2011;6:CD003510
7. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Available from: http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf [Accessed 14 November 2014]
8. Mandelbrot L, Berrebi A, Matheron S, et al. [HIV and pregnancy: 2013 guidelines from the French expert working group]. J Gynecol Obstet Biol Reprod (Paris) 2014;43:534-48
9. Taylor GP, Clayden P, Dhar J. British HIV Association guidelines for the management of HIV infection in pregnant women 2012. HIV Med 2012;13:87-157
10. Greig JM, Anderson J. Optimizing antiretroviral therapy for women living with HIV. Curr Opin Infect Dis 2014;27:46-52
11. Zidovudine for mother, fetus, and child: hope or poison? Lancet 1994;344:207-9
12. Chi BH, Bolton-Moore C, Holmes CB. Prevention of mother-to-child HIV transmission within the continuum of maternal, newborn, and child health services. Curr Opin HIV AIDS 2013;8:498-503
13. Mahy M, Stover J, Kiragu K, et al. What will it take to achieve virtual elimination of mother-to-child transmission of HIV? An assessment of current progress and future needs. Sex Transm Infect 2010;86:ii48-55
14. Antiretroviral drugs for treating women and preventing HIV infection in infants. WHO guidelines. Available from: http://www.who.int/hiv [Accessed 14 November 2014]
15. Global Aids Response Progress Reporting 2014. Available from: http://www.unaids. org/sites/default/files/media-asset/GARPR-2014-guidelines-en-0.pdf [Accessed 14 November 2014]
16. Else LJ, Taylor S, Back DJ, Khoo SH. Pharmacokinetics of antiretroviral drugs in anatomical sanctuary sites: the fetal compartment (placenta and amniotic fluid). Antivir Ther 2011;16:1139-47
17. Tomi M, Nishimura T, Nakashima E. Mother-to-fetus transfer of antiviral drugs and the involvement of transporters at the placental barrier. J Pharm Sci 2011;100:3708-18
18. Chappuy H, Treluyer JM, Jullien V, et al. Maternal-fetal transfer and amniotic fluid accumulation of nucleoside analogue reverse transcriptase inhibitors in human immunodeficiency virus-infected pregnant women. Antimicrob Agents Chemother 2004;48:4332-6
19. Fleming TR. Evaluating the safety of interventions for prevention of perinatal transmission of HIV. Ann N Y Acad Sci 2000;918:201-11
20. Dauby N, Goetghebuer T, Kollmann TR, et al. Uninfected but not unaffected: chronic maternal infections during pregnancy, fetal immunity, and susceptibility to postnatal infections. Lancet Infect Dis 2012;12:330-40
21. Afran L, Garcia Knight M, Nduati E, et al. HIV-exposed uninfected children: a growing population with a vulnerable immune system? Clin Exp Immunol 2014;176:11-22
22. Taron-Brocard C, Le Chenadec J, Faye A, et al. Increased risk of serious bacterial infections due to maternal immunosuppression in HIV-exposed uninfected infants in a European country. Clin Infect Dis 2014;59:1332-45
23. European Collaborative S, Swiss M; Child HIVCS. Combination antiretroviral therapy and duration of pregnancy. AIDS 2000;14:2913-20
24. Zack RM, Golan J, Aboud S, et al. Risk factors for preterm birth among HIV-infected tanzanian women: a prospective study. Obstet Gynecol Int 2014;2014:261689
25. Ezechi OC, David AN, Gab-Okafor CV, et al. Incidence of and socio-biologic risk factors for spontaneous preterm birth in HIV positive Nigerian women. BMC Pregnancy Childbirth 2012;12:93
26. Van der Merwe K, Hoffman R, Black V, et al. Birth outcomes in South African women receiving highly active antiretroviral therapy: a retrospective observational study. J Int AIDS Soc 2011;14:42
27. Tuomala RE, Watts DH, Li D, et al. Improved obstetric outcomes and few maternal toxicities are associated with antiretroviral therapy, including highly active antiretroviral therapy during pregnancy. J Acquir Immune Defic Syndr 2005;38:449-73
28. Townsend CL, Cortina-Borja M, Peckham CS, Tookey PA. Antiretroviral therapy and premature delivery in diagnosed HIV-infected women in the United Kingdom and Ireland. AIDS 2007;21:1019-26
29. Schulte J, Dominguez K, Sukalac T, Pediatric Spectrum of HIVDC. Declines in low birth weight and preterm birth among infants who were born to HIV-infected women during an era of increased use of maternal antiretroviral drugs: pediatric Spectrum of HIV Disease, 1989-2004. Pediatrics 2007;119:e900-6
30. Ravizza M, Martinelli P, Bucceri A, et al. Treatment with protease inhibitors and coinfection with hepatitis C virus are independent predictors of preterm delivery in HIV-infected pregnant women. J Infect Dis 2007;195:913-14
31. Kourtis AP, Schmid CH, Jamieson DJ, Lau J. Use of antiretroviral therapy in pregnant HIV-infected women and the risk of premature delivery: a meta-analysis. AIDS 2007;21:607-15
32. Patel K, Shapiro DE, Brogly SB, et al. Prenatal protease inhibitor use and risk of preterm birth among HIV-infected women initiating antiretroviral drugs during pregnancy. J Infect Dis 2010;201:1035-44
33. Lopez M, Figueras F, Hernandez S, et al. Association of HIV infection with spontaneous and iatrogenic preterm delivery: effect of HAART. AIDS 2012;26:37-43
34. Watts DH, Williams PL, Kacanek D, et al. Combination antiretroviral use and preterm birth. J Infect Dis 2013;207:612-21
35. Sibiude J, Warszawski J, Tubiana R, et al. Premature delivery in HIV-infected women starting protease inhibitor therapy during pregnancy: role of the ritonavir boost? Clin Infect Dis 2012;54:1348-60
36. Kesho Bora Study Group. de Vincenzi I. Triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV-1 (Kesho Bora study): a randomised controlled trial. Lancet Infect Dis 2011;11:171-80
37. Powis KM, Kitch D, Ogwu A, et al. Increased risk of preterm delivery among HIV-infected women randomized to protease versus nucleoside reverse transcriptase inhibitor-based HAART during pregnancy. J Infect Dis 2011;204:506-14
38. Koss CA, Natureeba P, Plenty A, et al. Risk factors for preterm birth among HIV-infected pregnant Ugandan women randomized to lopinavir/ritonavir-or efavirenz-based antiretroviral therapy. J Acquir Immune Defic Syndr 2014;67:128-35
39. Chen JY, Ribaudo HJ, Souda S, et al. Highly active antiretroviral therapy and adverse birth outcomes among HIV-infected women in Botswana. J Infect Dis 2012;206:1695-705
40. Ndirangu J, Newell ML, Bland RM, Thorne C. Maternal HIV infection associated with small-for-gestational age infants but not preterm births: evidence from rural South Africa. Hum Reprod 2012;27:1846-56
41. Briand N, Mandelbrot L, Le Chenadec J, ANRS French Perinatal Cohort. No relation between in-utero exposure to HAART and intrauterine growth retardation. AIDS 2009;23:1235-43
42. Jao J, Abrams EJ. Metabolic complications of in utero maternal HIV and antiretroviral exposure in HIV-exposed infants. Pediatr Infect Dis J 2014;33:734-40
43. Newschaffer CJ, Cocroft J, Anderson CE, et al. Prenatal zidovudine use and congenital anomalies in a medicaid population. J Acquir Immune Defic Synd 2000;24:249-56
44. Townsend CL, Willey BA, Cortina-Borja M, et al. Antiretroviral therapy and congenital abnormalities in infants born to HIV-infected women in the UK and Ireland, 1990-2007. Aids 2009;23:519-24
45. Brogly SB, Abzug MJ, Watts DH, et al. Birth defects among children born to human immunodeficiency virus-infected women: pediatric AIDS clinical trials protocols 219 and 219C. Pediatr Infect Dis J 2010;29:721-7
46. Watts DH, Huang S, Culnane M, et al. Birth defects among a cohort of infants born to HIV-infected women on antiretroviral medication. J Perinat Med 2011;39:163-70
47. Knapp KM, Brogly SB, Muenz DG, et al. Prevalence of congenital anomalies in infants with in utero exposure to antiretrovirals. Pediatr Infect Dis J 2012;31:164-70
48. Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry international interim report for 1 Jan 1989-31 July 2013. 2013. Available from: http://www.APRegistry.com [Accessed 14 November 2014]
49. Gibb DM, Kizito H, Russell EC, et al. DART trial team. Pregnancy and infant outcomes among. HIV-infected women taking long-term ART with and without tenofovir in the DART trial. PLoS Med 2012;9:e1001217
50. Food and Drug Administration. Sustiva drug label. Available from: http://www.accessdata.fda.gov/drugsatfda-docs/label/2010/021360s024lbl.pdf [Accessed 14 November 2014]
51. Ford N, Mofenson L, Shubber Z, et al. Safety of efavirenz in the first trimester of pregnancy: an updated systematic review and meta-analysis. AIDS 2014;28:S123-31
52. Sibiude J, Mandelbrot L, Blanche S, et al. Association between prenatal exposure to antiretroviral therapy and birth defects: an analysis of the French perinatal cohort study (ANRS CO1/CO11). Plos Med 2014;11:e1001635
53. Gideon K. editor. Maternal-Fetal Toxicology: a Clinician's Guide (Medical Toxicology). Marcel DEKKER, New York (USA)-Basel (CH);2001
54. Dryden-Peterson S, Shapiro RL, Hughes MD, et al. Increased risk of severe infant anemia after exposure to maternal HAART. Botswana. J Acquir Immune Defic Syndr 2011;56:428-36
55. Mandelbrot L, Landreau-Mascaro A, Rekacewicz C, Agence Nationale de Recherches sur le SIDA (ANRS) 075 Study Group. Lamivudine-zidovudine combination for prevention of maternal-infant transmission of HIV-1. JAMA 2001;285:2083-93
56. Andre-Schmutz I, Dal-Cortivo L, Six E, et al. Genotoxic signature in cord blood cells of newborns exposed in utero to a zidovudine-based antiretroviral combination. J Infect Dis 2013;208(2):235-43
57. Scalfaro P, Chesaux JJ, Buchwalder PA, et al. Severe transient neonatal lactic acidosis during prophylactic zidovudine treatment Intensive Care. Med 1998;24:247-50
58. Noguera A, Fortuny C, Munoz-Almagro C, et al. Hyperlactatemia in human immunodeficiency virus-uninfected infants who are exposed to antiretroviral. Pediatrics 2004;114:e598-603
59. Alimenti A, Burdge DR, Ogilvie GS, et al. Lactic acidemia in human immunodeficiency virus-uninfected infants exposed to perinatal antiretroviral therapy. Pediatr Infect Dis J 2003;22:782-9
60. Tarantal AF, Castillo A, Ekert JE, et al. Fetal and maternal outcome after administration of tenofovir to gravid rhesus monkeys (Macaca mulatta). J Acquir Immune Defic Syndr 2002;29:207-20
61. Siberry GK, Jacobson DL, Kalkwarf H, et al. Lower newborn bone mineral content (BMC) associated with maternal use of tenofovir disoproxil fumarate (TDF) [abstract 79]. CROI; Boston; 2014
62. Chasela CS, Hudgens MG, Jamieson DJ, BAN Study Group. Maternal or infant antiretroviral drugs to reduce HIV-1 transmission. N Engl J Med 2010;362:2271-81
63. Decloedt EH, Maartens G. Neuronal toxicity of efavirenz: a systematic review. Expert Opin Drug Saf 2013;12:841-6
64. Arendt G, de Ncker D, von Giesen HJ, Nolting T. Neuropsychiatric side effects of efavirenz therapy. Expert Opin Drug Saf 2007;6:147-54
65. Simon A, Warszawski J, Kariyawasam D, ANRS French Perinatal Cohort Study Group. Association of prenatal and postnatal exposure to lopinavir-ritonavir and adrenal dysfunction among uninfected infants of HIV-infected mothers. JAMA 2011;306:70-8
66. McArthur MA, Kalu SU, Foulks AR, et al. Twin preterm neonates with cardiac toxicity related to lopinavir/ritonavir therapy. Pediatr Infect Dis J 2009;28:1127-9
67. Lopriore E, Rozendaal L, Gelinck LB, et al. Twins with cardiomyopathy and complete heart block born to an HIV-infected mother treated with HAART. AIDS 2007;21:2564-5
68. Available from: http://www.fda;gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm246167.htm [Accessed 14 November 2014]
69. Mandelbrot L, Mazy F, Floch-Tudal C, et al. Atazanavir in pregnancy: impact on neonatal hyperbilirubinemia. Eur J Obstet Gynecol Reprod Biol 2011;157:18-21
70. Blanche S, Tardieu M, Rustin P, et al. Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues. Lancet 1999;354:1084-9
71. Brogly SB, DiMauro S, Van Dyke RB, et al. Transplacental nucleoside analogue exposure and mitochondrial parameters in HIV-uninfected children. AIDS Res Hum Retroviruses 2011;27:777-83
72. Divi RL, Leonard SL, Kuo MM, et al. Cardiac mitochondrial compromise in one year old Erythrocebus patas monkeys exposed in utero to nucleoside reverse transcriptase inhibitors. Cardiovasc Toxicol 2005;5:333-46
73. Ross AC, Leong T, Avery A, et al. Effects of in utero antiretroviral exposure on mitochondrial DNA levels, mitochondrial function and oxidative stress. HIV Med 2012;13:98-106
74. Gardner K, Hall PA, Chinnery PF, Payne BA. HIV treatment and associated mitochondrial pathology: review of 25 years of in vitro, animal, and human studies. Toxicol Pathol 2013;42:811-22
75. Divi RL, Einem TL, Fletcher SL, et al. Progressive mitochondrial compromise in brains and livers of primates exposed in utero to nucleoside reverse transcriptase inhibitors (NRTIs). Toxicol Sci 2010;118:191-201
76. Olivero OA, Shearer GM, Chougnet CA, et al. Incorporation of zidovudine into leukocyte DNA from HIV-1-positive adults and pregnant women, and cord blood from infants exposed in utero. AIDS 1999;13:919-25
77. Escobar PA, Olivero OA, Wade NA, et al. Genotoxicity assessed by the comet and GPA assays following in vitro exposure of human lymphoblastoid cells (H9) or perinatal exposure of mother-child pairs to AZT or AZT-3TC. Environ Mol Mutagen 2007;48:330-43
78. Witt KL, Cunningham CK, Patterson KB, et al. Elevated frequencies of micronucleated erythrocytes in infants exposed to zidovudine in utero and postpartum to prevent mother-to-child transmission of HIV. Environ Mol Mutagen 2007;48:322-9
79. Senda S, Blanche S, Costagliola D, et al. Altered heterochromatin organization after perinatal exposure to zidovudine. Antivir Ther 2007;12:179-87
80. Olivero OA, Torres LR, Gorjifard S, et al. Perinatal exposure of patas monkeys to antiretroviral nucleoside reverse-transcriptase inhibitors induces genotoxicity persistent for up to 3 years of age. J Infect Dis 2013;208:244-8
81. Vivanti A, Cuccuini W, Luce S, et al. Comparative genotoxic signature in cord blood cells from neonates exposed to AZT or TDF in utero [abstract P-T2 379]. 21th Conference on Retroviruses and Opportunistic Infections CROI;3-6 March 2014;Boston, USA; AIDS 2015, in press
82. Barret B, Tardieu M, Rustin P, et al. Persistent mitochondrial dysfunction in HIV-1-exposed but uninfected infants: clinical screening in a large prospective cohort. AIDS 2003;17:1769-85
83. Crain MJ, Chernoff MC, Oleske JM, et al. Possible mitochondrial dysfunction and its association with antiretroviral therapy use in children perinatally infected with HIV. J Infect Dis 2010;202:291-301
84. Nozyce ML, Huo Y, Williams PL, et al. Safety of in utero and neonatal antiretroviral exposure: cognitive and Academic outcomes in HIV-exposed, uninfected children 5-13 years of age. Pediatr Infect Dis J 2014;33:1128-33
85. Lipshultz SE, Shearer WT, Thompson B, et al. Cardiac effects of antiretroviral therapy in HIV-negative infants born to HIV-positive mothers: the NHLBI CHAART-1 cohort study. J Am Coll Cardiol 2011;57:76-85
86. Cade WT, Waggoner AD, Hubert S, et al. Reduced diastolic function and left ventricular mass in HIV-negative pre-adolescent children exposed to antiretroviral therapy in Utero. AIDS 2012;26:2053-8
87. Sibiude J, Le Chenadec J, Bonnet D, et al. In utero exposure to zidovudine and neonatal heart abnormalities in the ANRS-EPF/PRIMEVA studies [abstract 862]. 21th Conference on Retroviruses and Opportunistic Infections CROI;3-6 March 2014; Boston, USA
88. Torres SM, Divi RL, Walker DM, et al. In utero exposure of female CD-1 mice to AZT and/or 3TC: II. Persistence of functional alterations in cardiac tissue. Cardiovasc Toxicol 2010;10:87-99
89. Divi RL, Leonard SL, Kuo MM, et al. Cardiac mitochondrial compromise in 1-yr-old Erythrocebus patas monkeys perinatally-exposed to nucleoside reverse transcriptase inhibitors. Cardiovasc Toxicol 2005;5:333-46
90. Payne BAI, Wilson IJ, Hateley CA, et al. Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations. Nat Genet 2011;43:806-10
91. Le Chenadec J, Mayaux MJ, Guihenneuc-Jouyaux C, Blanche S; Enquête Perinatale Française Study Group. Perinatal antiretroviral treatment and hematopoiesis in HIV-uninfected infants. AIDS 2003;17:2053-61
92. Pacheco SE, McIntosh K, Lu M, et al. Effect of perinatal antiretroviral drug exposure on hematologic values in HIV-uninfected children: an analysis of the women and infants transmission study. J Infec Dis 2006;194:1089-97
93. Bunders MJ, Bekker V, Scherpbier HJ, et al. Haematological parameters of HIV-1-uninfected infants born to HIV-1-infected mothers. Acta Paediatr 2005;94:1571-7
94. Benhammou V, Warszawski J, Bellec S, et al. Incidence of cancer in children perinatally exposed to nucleoside reverse transcriptase inhibitors. AIDS 2008;22:2165-77
95. Tubiana R, Mandelbrot L, Le Chenadec J, et al. Lopinavir/ritonavir monotherapy as a nucleoside analogue-sparing strategy to prevent HIV-1 mother-to-child transmission: the ANRS 135 PRIMEVA phase 2/3 randomized trial. Clin Infect Dis 2013;57:891-902
96. Nielsen-Saines K, Watts DH, Veloso VG, et al. NICHD HPTN 040/PACTG 1043 Protocol Team. Three postpartum antiretroviral regimens to prevent intrapartum HIV infection. N Engl J Med 2012;366:2368-79
97. Liu KC, Farahani M, Mashamba T, et al. Pregnancy outcomes and birth defects from an antiretroviral drug safety study of women in South Africa and Zambia. AIDS 2014;28:2259-68
98. Goodman A, Schorge J, Greene MF. The long-term effects of in utero exposures-the DES story. N Engl J Med 2011;364:2083-4